Novel associations between activating killer-cell immunoglobulin-like receptor genes and childhood leukemia.

Abstract

Acute lymphoblastic leukemia of pre-B cells (pre-B ALL) is the most frequent form of leukemia affecting children in Western countries. Evidence is accumulating that genetic factors play an important role in conferring susceptibility/resistance to leukemia in children. In this regard, activating killer-cell immunoglobulin-like receptor (KIR) genes are of particular interest. Humans may inherit different numbers of the 6 distinct activating KIR genes. Little is known about the impact of this genetic variation on the innate susceptibility or resistance of humans to the development of B-ALL. We addressed this issue by performing a case-control study in Canadian children of white origin. Our results show that harboring activating KIR genes is associated with reduced risk for developing B-ALL in these children. Of the 6 activating KIR genes, KIR2DS2 was maximally associated with decreased risk for the disease (P = 1.14 × 10(-7)). Furthermore, our results showed that inheritance of a higher number of activating KIR genes was associated with significant reductions in risk for ALL in children. These results were also consistent across different ALL phenotypes, which included children with pre-T cell ALL. Our study provides novel insights concerning the pathogenesis of childhood leukemia in white children and has implications for the development of new immunotherapies for this cancer.

• Authors: Zaema Almalte, Suzanne Samarani, Alexandre Iannello, Olfa Debbeche, Michel Duval, Claire Infante-Rivard, Devendra K Amre, Daniel Sinnett, Ali Ahmad
• Journal: Blood (Blood) Vol. 118 Issue 5 Pg. 1323-8 (Aug 04 2011) ISSN: 1528-0020 [Electronic] United States
• PMID: 21613255 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, KIR

Topics

• Age of Onset
• Case-Control Studies
• Child
• Child, Preschool
• Female
• Genetic Predisposition to Disease
• Genome-Wide Association Study
• Genotype
• Humans
• Infant
• Infant, Newborn
• Leukemia (epidemiology, genetics)
• Male
• Precursor B-Cell Lymphoblastic Leukemia-Lymphoma (epidemiology, genetics)
• Precursor T-Cell Lymphoblastic Leukemia-Lymphoma (epidemiology, genetics)
• Receptors, KIR (genetics, physiology)